Drug-drug interactions are not uncommon during antiepileptic therapy. These interactions constitute a clinical problem due to a relatively narrow therapeutic index for antiepileptic drugs. Many of these interactions are a result of altered drug metabolism. Most recently, unexpected drug-drug interactions were observed during Antiepileptic Drug Development clinical trials for two promising candidate antiepileptic drugs (ADD 35002, ADD 03055). When either of these drugs was added to the existing phenytoin and carbamazepine therapy, a dramatic rise in plasma levels of the latter drugs was observed. An in vitro rat hepatic microsomal system is being used to study interactions between antiepileptic drugs. A standard Michaelis-Menten approach is being applied to define kinetic parameters Km, Vmax, and Ki for microsomal metabolism of anticonvulsants. This in vitro systems is being used to elucidate mechanisms behind these interactions. It may also be potentially useful as a screening procedure for predicting the interactions.